The HPV16 E2 protein is uniformly expressed during productive viral infection. It has been reported that T cell responses to E2 are inversely correlated with risk of cervical cancer. E2 is an important target for immune-mediated clearance of HPV mediated cervical lesions. Our previous study demonstrated that immune response to HPV E2 could be induced by multiple immunizations with the combined chimeric virus-like particles and E2 peptides (J. Int. Cancer 2006). As CD8+ T cell response to E2 can be induced only with multiple immunizations. To enhance the immunogenicity of E2, we modified the E2 epitope 138-147 by substituting positions 139 and 140 from isoleucine-cysteine to leucine-alanine (E2-138-147LA). This modified peptide demonstrated a higher affinity for HLA-A2 in a T2 binding assay than the wild type one and induced a CD8+ T cell response by a signal peptide immunization (with GM-CSF and anti-CD40) in HLA-A2 transgenic mice. We have established a tumor cell line expressing a E2 protein. Spleen cells from mice immunized either with wild type or modified E2 peptide can lyse tumor cell line expressing E2. Thus, the E2 peptides' based vaccine has a potential to be considered as vaccine targeting early HPV16-imediated neoplastic lesions (NCI patent: E-155-2005 and a manuscript in preparation).